{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T09:13:25Z","timestamp":1788599605067,"version":"build-2803163510"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:00:00Z","timestamp":1770336000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:p>\n                    Although genetic factors contribute significantly to male infertility, the underlying mechanisms remain incompletely understood. Coiled-coil domain-containing protein 113 (\n                    <jats:italic toggle=\"yes\">CCDC113<\/jats:italic>\n                    ) encodes a coiled-coil domain-containing protein critical for the assembly of cilia and flagella. Using whole-exome sequencing, we identified biallelic\n                    <jats:italic toggle=\"yes\">CCDC113<\/jats:italic>\n                    mutations in two unrelated families affected by oligoasthenoteratozoospermia. The mutations (c.901A&gt;C; p.K301Q and c.404A&gt;C; p.E135A) cosegregated with infertility phenotypes and were associated with defective sperm flagella. Functional analyses demonstrated that these mutations led to less stable CCDC113 protein and severely disrupted axonemal structures in spermatozoa from our three human patients. We generated\n                    <jats:italic toggle=\"yes\">Ccdc113<\/jats:italic>\n                    knockout mice, which recapitulated the human infertility phenotypes, including abnormal sperm morphology, impaired motility, and defective spermatogenesis. Importantly, one patient achieved successful pregnancy by intracytoplasmic sperm injection, highlighting the translational potential of genetic diagnostics. These findings suggest that\n                    <jats:italic toggle=\"yes\">CCDC113<\/jats:italic>\n                    is essential for male fertility and contribute to the understanding of the genetic landscape of infertility, offering novel insights into its diagnosis and management.\n                  <\/jats:p>","DOI":"10.4103\/aja202585","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T05:00:22Z","timestamp":1770354022000},"page":"500-508","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":1,"title":["Loss-of-function mutations in Ccdc113 cause male infertility in both humans and mice"],"prefix":"10.4103","volume":"28","author":[{"given":"Hong-Tao","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Emergency Surgery, Sichuan Academy of Medical Sciences and Sichuan Provincial People\u2019s Hospital, University of Electronic Science and Technology, Chengdu 610072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fu-Lin","family":"Liu","sequence":"additional","affiliation":[{"name":"Sichuan Provincial Key Laboratory for Human Disease Gene Study, Center for Medical Genetics, Department of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People\u2019s Hospital, University of Electronic Science and Technology, Chengdu 610072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Xiao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Sichuan Academy of Medical Sciences & Sichuan Provincial People\u2019s Hospital, University of Electronic Science and Technology, Chengdu 610072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Emergency Surgery, Sichuan Academy of Medical Sciences and Sichuan Provincial People\u2019s Hospital, University of Electronic Science and Technology, Chengdu 610072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,2,6]]},"reference":[{"key":"R1-20260905","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1038\/s41585-018-0003-3","article-title":"Genetics of male infertility","volume":"15","author":"Krausz","year":"2018","journal-title":"Nat Rev Urol"},{"key":"R2-20260905","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/s41572-023-00459-w","article-title":"Male infertility","volume":"9","author":"Eisenberg","year":"2023","journal-title":"Nat Rev Dis Primers"},{"issue":"Suppl 1","key":"R3-20260905","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/humrep\/13.suppl_1.1","article-title":"Spermatogenesis","volume":"13","author":"de Kretser","year":"1998","journal-title":"Hum Reprod"},{"key":"R4-20260905","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.semcdb.2016.04.009","article-title":"Spermatogenesis in humans and its affecting factors","volume":"59","author":"Neto","year":"2016","journal-title":"Semin Cell Dev Biol"},{"key":"R5-20260905","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.3390\/genes15101315","article-title":"The molecular basis of multiple morphological abnormalities of sperm flagella and its impact on clinical practice","volume":"15","author":"Zhou","year":"2024","journal-title":"Genes (Basel)"},{"key":"R6-20260905","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1152\/physrev.00009.2020","article-title":"Sperm bauplan and function and underlying processes of sperm formation and selection","volume":"102","author":"Teves","year":"2022","journal-title":"Physiol Rev"},{"key":"R7-20260905","doi-asserted-by":"crossref","first-page":"R229","DOI":"10.1530\/REP-17-0536","article-title":"Sperm form and function: what do we know about the role of sexual selection?","volume":"155","author":"Lupold","year":"2018","journal-title":"Reproduction"},{"key":"R8-20260905","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/s10815-016-0652-1","article-title":"The axoneme: the propulsive engine of spermatozoa and cilia and associated ciliopathies leading to infertility","volume":"33","author":"Linck","year":"2016","journal-title":"J Assist Reprod Genet"},{"key":"R9-20260905","doi-asserted-by":"crossref","first-page":"216225","DOI":"10.1016\/j.canlet.2023.216225","article-title":"Regulatory network and targeted interventions for CCDC family in tumor pathogenesis","volume":"565","author":"Liu","year":"2023","journal-title":"Cancer Lett"},{"key":"R10-20260905","doi-asserted-by":"crossref","first-page":"2725","DOI":"10.1007\/s43032-021-00595-2","article-title":"Coiled-coil domain-containing (CCDC) proteins: functional roles in general and male reproductive physiology","volume":"28","author":"Priyanka","year":"2021","journal-title":"Reprod Sci"},{"key":"R11-20260905","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1007\/s10815-019-01509-7","article-title":"Characterization of CCDC103 expression profiles: further insights in primary ciliary dyskinesia and in human reproduction","volume":"36","author":"Pereira","year":"2019","journal-title":"J Assist Reprod Genet"},{"key":"R12-20260905","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1007\/s00439-022-02459-4","article-title":"Homozygous missense mutation in CCDC155 disrupts the transmembrane distribution of CCDC155 and SUN1, resulting in non-obstructive azoospermia and premature ovarian insufficiency in humans","volume":"141","author":"Wu","year":"2022","journal-title":"Hum Genet"},{"key":"R13-20260905","doi-asserted-by":"crossref","first-page":"e52775","DOI":"10.15252\/embr.202152775","article-title":"Male infertility-associated Ccdc108 regulates multiciliogenesis via the intraflagellar transport machinery","volume":"23","author":"Zhao","year":"2022","journal-title":"EMBO Rep"},{"key":"R14-20260905","first-page":"817","article-title":"Ccdc87 is critical for sperm function and male fertility","volume":"99","author":"Wang","year":"2018","journal-title":"Biol Reprod"},{"key":"R15-20260905","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00018-023-05025-x","article-title":"CCDC146 is required for sperm flagellum biogenesis and male fertility in mice","volume":"81","author":"Ma","year":"2023","journal-title":"Cell Mol Life Sci"},{"key":"R16-20260905","doi-asserted-by":"crossref","first-page":"dev200516","DOI":"10.1242\/dev.200516","article-title":"CCDC38 is required for sperm flagellum biogenesis and male fertility in mice","volume":"149","author":"Zhang","year":"2022","journal-title":"Development"},{"key":"R17-20260905","doi-asserted-by":"crossref","first-page":"3371","DOI":"10.1016\/j.cub.2023.06.079","article-title":"CCDC176 stabilizes microtubule doublets 1 and 9 to ensure proper sperm movement","volume":"33","author":"Liu","year":"2023","journal-title":"Curr Biol"},{"key":"R18-20260905","doi-asserted-by":"crossref","first-page":"e18215","DOI":"10.1111\/jcmm.18215","article-title":"CCDC157 is essential for sperm differentiation and shows oligoasthenoteratozoospermia-related mutations in men","volume":"28","author":"Zheng","year":"2024","journal-title":"J Cell Mol Med"},{"key":"R19-20260905","doi-asserted-by":"crossref","first-page":"nwad181","DOI":"10.1093\/nsr\/nwad181","article-title":"CCDC189 affects sperm flagellum formation by interacting with CABCOCO1","volume":"10","author":"Wang","year":"2023","journal-title":"Natl Sci Rev"},{"key":"R20-20260905","first-page":"4128","article-title":"Proteomic analysis of mammalian sperm cells identifies new components of the centrosome","volume":"127","author":"Firat-Karalar","year":"2014","journal-title":"J Cell Sci"},{"key":"R21-20260905","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1080\/15384101.2017.1315494","article-title":"Novel clades of the HU\/IHF superfamily point to unexpected roles in the eukaryotic centrosome, chromosome partitioning, and biologic conflicts","volume":"16","author":"Burroughs","year":"2017","journal-title":"Cell Cycle"},{"key":"R22-20260905","doi-asserted-by":"crossref","first-page":"e1009388","DOI":"10.1371\/journal.pgen.1009388","article-title":"Ccdc113\/Ccdc96 complex, a novel regulator of ciliary beating that connects radial spoke 3 to dynein g and the nexin link","volume":"17","author":"Bazan","year":"2021","journal-title":"PLoS Genet"},{"key":"R23-20260905","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/s41419-024-07036-3","article-title":"CCDC113 promotes colorectal cancer tumorigenesis and metastasis via TGF-beta signaling pathway","volume":"15","author":"Hou","year":"2024","journal-title":"Cell Death Dis"},{"key":"R24-20260905","doi-asserted-by":"crossref","first-page":"RP98016","DOI":"10.7554\/eLife.98016","article-title":"CCDC113 stabilizes sperm axoneme and head-tail coupling apparatus to ensure male fertility","volume":"13","author":"Wu","year":"2024","journal-title":"eLife"},{"key":"R27-20260905","doi-asserted-by":"crossref","first-page":"RP86845","DOI":"10.7554\/eLife.86845.3","article-title":"Lack of CCDC146, a ubiquitous centriole and microtubule-associated protein, leads to non-syndromic male infertility in human and mouse","volume":"12","author":"Muronova","year":"2024","journal-title":"Elife"},{"key":"R28-20260905","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1091\/mbc.E17-08-0510","article-title":"DRC2\/CCDC65 is a central hub for assembly of the nexin-dynein regulatory complex and other regulators of ciliary and flagellar motility","volume":"29","author":"Bower","year":"2018","journal-title":"Mol Biol Cell"},{"key":"R29-20260905","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1111\/cge.14459","article-title":"CCDC65, encoding a component of the axonemal Nexin-Dynein regulatory complex, is required for sperm flagellum structure in humans","volume":"105","author":"Jreijiri","year":"2024","journal-title":"Clin Genet"},{"key":"R30-20260905","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1038\/s41586-023-06140-2","article-title":"Axonemal structures reveal mechanoregulatory and disease mechanisms","volume":"618","author":"Walton","year":"2023","journal-title":"Nature"}],"container-title":["Asian Journal of Andrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/aja202585","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T09:00:34Z","timestamp":1788598834000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/aja202585"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,6]]},"references-count":28,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.4103\/aja202585","relation":{},"ISSN":["1008-682X","1745-7262"],"issn-type":[{"value":"1008-682X","type":"print"},{"value":"1745-7262","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,6]]},"assertion":[{"value":"2025-04-05","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-13","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}